Acetone → HCID 57781092, compound

Participants

Reaction Conditions

Reaction Steps

N,N-Diethyl-3,4-difluoro-2-imidazol-1-ylmethyl-benzamide (0.832 g, 2.695 mmol) is dissolved in THF (15 mL) and cooled to −78° C. LHMDS (1.0M in THF, 4.0 mL, 4.0 mmol) is added over 5 min, resulting in a dark brown solution. After another 10 min, acetone (0.79 g, 13.47 mmol) is added. After 30 min, the mixture is quenched with a pH 7 aqueous buffer and extracted twice with ethyl acetate. The combined organic phase is dried over magnesium sulfate and concentrated in vacuo to give a brown residue, which is redissolved in dioxane (25 mL). 1M aqueous KOH (13.5 mL, 13.5 mmol) is added. The solution is heated to 65° C. After 3 h, the mixture is cooled with a water bath, and acidified to pH=1 with conc. HCl. The mixture is heated to 65° C. After 1 h, the mixture is diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate, water and brine, dried over magnesium sulfate and filtered through a cotton plug. Concentration in vacuo gives a residue which is purified by silica gel flash chromatography (methylene chloride-methanol, 49:1 to 97:3) to give 5,6-difluoro-4-imidazol-1-yl-3,3-dimethyl-isochroman-1-one as an oil, which is converted to its HCl salt to give a solid; MS (ESI) m/z 279.1 (M+H); 1H NMR (400 MHz, MeOD) of the HCl salt, δ ppm 1.34 (s, 3 H), 1.61 (s, 3 H), 6.29 (s, 1 H), 7.46 (br. s., 1 H), 7.53 (br. s., 1 H), 7.66-7.75 (m, 1 H), 8.20 (ddd, J=8.8, 4.6, 1.6 Hz, 1 H), 8.79 (br. s., 1 H).

Provenance & Evidence